Efforts in this project have been directed at the organ culture of lenses that are genetically precataractous. The purpose is to determine if cataract development in organ culture follows a similar course as observed in vivo. The model currently in use is the lens from a transgenic mouse that has the HIV-1 protease linked to the alpha-A-crystallin promoter. These lenses become cataractous about 24 days after birth. In organ culture, the changes observed to the proteins are similar to those in vivo. Although the cataract is observed a few days before the one in vivo, progression of the cataract is remarkably analogous in both cases. This is the first demonstration that a "programmed" cataract can be obtained in organ culture without the use of any additional agents. We have also demonstrated that the cataract can be delayed in organ culture by using an inhibitor to cysteine protease. Future work will concentrate on developing this model so that it can be used to test anticataract agents.